(103 days)
The NMP22 BladderChek Test is indicated for professional and prescription home use as an aid in monitoring bladder cancer patients, in conjunction with standard diagnostic procedures.
The NMP22 BladderChek Test for nuclear matrix protein NMP22 is an immunochromatographic assay utilizing monoclonal antibodies in a lateral flow strip encased in plastic. Two different antibodies are used, one as a capture and one as a reporter antibody. Unprocessed patient urine is added to the sample well of the cartridge and allowed to react with the colloidal gold conjugated reporter antibody. If the antigen is present in urine, it will interact with the reporter conjugate to form an immune complex. The reaction mixture flows through the membrane, which contains zones of immobilized antibodies. In the Test (T) zone, antigen-conjugate complexes are trapped by the capture antibody, forming a visible line if the concentration of antigen in urine is elevated. The procedural Control (C) zone contains an immobilized goat anti-mouse IgG-specific antibody that will capture the conjugated antibody independently of the presence or absence of the antigen, thereby always producing a visible line in the Control window. This procedural control assures the operator that each device is working properly.
Here's a summary of the acceptance criteria and study details for the NMP22 BladderChek™ Kit, based on the provided text:
1. Acceptance Criteria and Reported Device Performance
Although explicit "acceptance criteria" (numerical thresholds that must be met for approval) are not directly stated in the summary, the overall performance goals are implied by successful demonstration of substantial equivalence to the predicate device and satisfactory clinical performance. The table below presents the clinical performance metrics reported for the NMP22 BladderChek™ Test and, for comparison, the predicate device.
| Performance Metric | Acceptance Criteria (Implied) | Reported Device Performance (NMP22 BladderChek™) | Predicate Device Performance (BTA Stat) |
|---|---|---|---|
| Clinical Sensitivity | Comparable or better than predicate | 45.9% (95% CI: 35.8%, 56.3%) (45/98) | 67% (95% CI: 60%, 73%) |
| Clinical Specificity | Comparable or better than predicate | 86.3% (95% CI: 83.2%, 89.0%) (492/570) | 70% (95% CI: 61%, 79%) |
| Positive Predictive Value (PPV) | Comparable or better than predicate | 36.6% (95% CI: 28.1%, 45.8%) at 14.7% incidence | 19.8% to 48.8% (theoretical range due to retrospective data) |
| Negative Predictive Value (NPV) | Comparable or better than predicate | 90.3% (95% CI: 87.5%, 92.6%) at 14.7% incidence | (Not calculated for predicate due to retrospective data) |
| Overall Accuracy | Comparable or better than predicate | 80.3% | 67.9% |
| Reproducibility (Lab Techs) | High concordance across lots, users, and days | 99.2% overall correct reads (1786/1800) | "Nearly total agreement" (near cut-off exceptions) |
| Reproducibility (Lay vs. Professional) | High concordance | 100% concordance (lay vs. professional) on precision panel | N/A |
| Concordance (Lay vs. Professional – Real-world) | High agreement | 96.4% (professional re-read lay user device); 95.6% (professional re-test lay user urine) | N/A |
| Concordance with Microplate Test | Good concordance | 91.2% overall (198/217) | N/A |
Summary of the Study Proving Acceptance Criteria:
The device's performance was evaluated through non-clinical and clinical studies to demonstrate substantial equivalence to the predicate device, BTA Stat.
2. Sample Size Used for the Test Set and Data Provenance:
-
Clinical Test Set:
- Sample Size: 668 patients.
- Data Provenance: Prospective clinical trial conducted at 23 sites. The country of origin is not explicitly stated but implied to be the US given the submission to the FDA.
-
Non-Clinical Test Set (Reproducibility by Laboratory Technicians):
- Sample Size: 150 individual reads per panel level (3 readers x 10 devices per panel x 5 days) for 4 NMP22 levels (0, 5, 15, 25 U/mL). Total 600 reads per lot. Experiment conducted on three separate lots, so 1800 total unique device reads.
- Data Provenance: Not specified, but likely internal lab studies.
-
Non-Clinical Test Set (Reproducibility by Lay Users Compared to Professional Readers):
- Sample Size: 5 lay readers (10 results per level) and 2 professional readers (10 results per level) for a three-level precision panel (2, 10, 15 U/mL). In total, 50 lay user results and 20 professional reader results.
- Data Provenance: Not specified, but likely internal lab studies.
-
Non-Clinical Test Set (Performance of Lay Users Compared to Professionals – Field Studies):
- Sample Size: 137 volunteers (aged 50+), across 3 sites.
- Data Provenance: Field studies at three unspecified locations.
-
Non-Clinical Test Set (Concordance of NMP22 BladderChek and NMP22 Test Kit (microplate)):
- Sample Size: 217 voided urine samples.
- Data Provenance: Urology clinics.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications:
-
Clinical Test Set:
- Number of Experts: Not explicitly stated, but the ground truth for bladder cancer status was determined by physicians conducting cystoscopies and subsequent pathological examination of resected lesions. These are highly qualified medical professionals (e.g., urologists and pathologists).
- Qualifications: "Physicians conducting the cystoscopies" and "pathologically determined to be malignant."
-
Non-Clinical Test Set (Reproducibility):
- Laboratory Technicians: 3 laboratory technicians. Qualifications not specified, but implied to be trained in laboratory procedures.
- Professional Readers (Lay User Reproducibility): 2 professional readers. Qualifications not specified.
4. Adjudication Method for the Test Set:
-
Clinical Test Set: The primary ground truth was established by cystoscopy findings, confirmed by pathology for resected lesions. Physicians were blinded to the device results, suggesting an independent assessment of ground truth. There is no mention of a specific adjudication method (like 2+1 or 3+1) among multiple experts for establishing the cancer status itself, rather it relies on standard medical diagnostic procedures.
-
Non-Clinical Test Set (Reproducibility):
- For the lab technician reproducibility, the ground truth was based on the known NMP22 concentration of the prepared specimen panels (0, 5, 15, 25 U/mL).
- For lay user vs. professional reproducibility, the ground truth was based on the known NMP22 concentration of the prepared samples (2, 10, 15 U/mL). Concordance was measured between readers rather than against an external adjudicator.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study:
- No specific MRMC comparative effectiveness study was mentioned comparing human readers with and without AI assistance (as the device is a diagnostic kit, not an AI).
- However, the study did involve a comparison of lay users vs. professional readers using the device, which is a form of multi-reader evaluation. There was 100% concordance between lay and professional readers on precision panels and high concordance (95.6% - 96.4%) in field studies for real urine samples, indicating that the device design allows for consistent interpretation across different user types.
6. Standalone Performance:
- Yes, a standalone performance study was done. The entire clinical study assessed the performance of the NMP22 BladderChek™ Test alone (algorithm/device only, without human-in-the-loop assistance influencing the result) against the cystoscopy/pathology ground truth. The reported sensitivity, specificity, PPV, and NPV are all measures of this standalone performance.
7. Type of Ground Truth Used:
-
Clinical Test Set: The ground truth was based on cystoscopy findings, with confirmation by pathology for malignant lesions. "Patients were considered negative if no tumor was seen endoscopically, or, if a lesion was seen, was pathologically determined to be nonmalignant. Patients were considered positive for bladder cancer if a tumor was seen during cystoscopy, and, if removed was pathologically determined to be malignant." This is a combination of observational medical findings and definitive pathological diagnosis.
-
Non-Clinical Test Set (Reproducibility): The ground truth was based on known concentrations of NMP22 in prepared urine specimens.
8. Sample Size for the Training Set:
- Not explicitly stated. The submission describes validation studies but does not detail a separate training set size for the development of the device itself (e.g., for antibody selection or cut-off determination). This is typical for a diagnostic kit where the "training" (e.g., cut-off determination) often happens during product development and optimization, rather than a distinct "training set" in the context of an AI algorithm.
9. How the Ground Truth for the Training Set Was Established:
- Not explicitly detailed as a distinct training set is not explicitly mentioned. For the development and optimization of such a diagnostic device (e.g., determining the NMP22 threshold for a positive result like 10 U/mL mentioned in the microplate comparison), ground truth would typically be established similarly to the clinical test set: using urine samples from known bladder cancer patients and healthy controls, confirmed by established diagnostic methods like cystoscopy and pathology. The 10 U/mL cutoff for the NMP22 microplate test is stated, implying that this was an established threshold for a positive result.
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510(k) SUMMARY
This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.
The assigned 510(k) number is: K021231
| Name: | Matritech, Inc.330 Nevada St.Newton, MA 02460 |
|---|---|
| Contact: | Melodie R. Domurad PhD617 928 0820 ext 265mdomurad@matritech.com |
| Date: | April 15, 2002 |
| Catalog Number: | D1200 24-test kitD1201 1-test kitD1250 Control kit |
| Device Name: | NMP22® BladderChek™ KitNMP22® Control Kit |
| Common: | NMP22 BladderChek |
| Classification: | Class II |
| Manufacturer: | Unotech Diagnostics, Inc.2235 Polvorosa Ave.Suite 220San Leandro, CA 94577 |
| Registration Number: | 1225597 Matritech, Inc.2953160 Unotech Diagnostics, Inc |
| Substantially Equivalent | RTA Stat Test |
Predicate Device
Description of Device
The NMP22 BladderChek Test is an in vitro diagnostic assay for the qualitative detection of the nuclear matrix protein NMP22 in human urine.
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Intended Use
The Matritech NMP22 BladderChek Test is indicated for professional and prescription home use as an aid in monitoring bladder cancer patients, in conjunction with standard diagnostic procedures.
Summary and Explanation of the Test
The NMP22 BladderChek Test for nuclear matrix protein NMP22 is an immunochromatographic assay utilizing monoclonal antibodies in a lateral flow strip encased in plastic. Two different antibodies are used, one as a capture and one as a reporter antibody. Unprocessed patient urine is added to the sample well of the cartridge and allowed to react with the colloidal gold conjugated reporter antibody. If the antigen is present in urine, it will interact with the reporter conjugate to form an immune complex. The reaction mixture flows through the membrane, which contains zones of immobilized antibodies. In the Test (T) zone, antigen-conjugate complexes are trapped by the capture antibody, forming a visible line if the concentration of antigen in urine is elevated. The procedural Control (C) zone contains an immobilized goat anti-mouse IgG-specific antibody that will capture the conjugated antibody independently of the presence or absence of the antigen, thereby always producing a visible line in the Control window. This procedural control assures the operator that each device is working properly.
Substantial Equivalence to Predicate Device
Both the NMP22 BladderChek Test and BTA Stat are single use, in vitro diagnostic devices for detecting recurrence in patients with a history of bladder cancer. The assay reactions for the two devices are immunochromatographic, utilizing monoclonal antibodies, and produce qualitative results. Both detect analytes from voided urine. Targeted environment for the two tests is prescription home use. The NMP22 BladderChek Test detects the nuclear matrix protein NMP22, and the BTA Stat Test detects Bladder Tumor Antigen.
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| NMP22 BladderChekK021231 | BTA StatK974845 & K964151 | |
|---|---|---|
| Intended Use | Aid in the monitoring of bladdercancer patients in conjunctionwith standard diagnosticprocedures | Aid in the management ofbladder cancer patients inconjunction with cystoscopy |
| Sample Matrix | Voided urine | Voided urine |
| Procedural Steps | Add 4 drops of urine | Add 5 drops of urine |
| Result Interpretation | +/-, Qualitative | +/-, Qualitative |
| Analyte Measured | NMP22Nuclear Matrix Protein | BTABladder Tumor Antigen |
| Targeted Environment | Professional and PrescriptionHome Use | Laboratory and PrescriptionHome Use |
| Assay Reaction | Immunochromatographic | Immunochromatographic |
Non-Clinical Tests
Reproducibility by Laboratory Technicians
Precision studies were conducted to determine the percent of devices correctly read. Specimen panels with NMP22 levels of 0, 5, 15, and 25 U/mL were used. Three laboratory technicians each read ten devices per level in random order, (40 devices/lab tech) for five different days. This produced 150 individual reads per panel level (3 readers x 10 devices per panel x 5 days). The experiment was conducted on three separate lots of devices.
The percent of correctly read NMP22 BladderChek devices was very consistent across lots (n=3), lab techs (n=3), and days (n=5), where urine specimens with NMP22 levels of 0 and 5 U/mL should have been read as negative and urine specimens with NMP22 levels of 15 and 25 U/mL should have been read as positive.
The overall percent of correct reads was 99.2% (1786/1800). Twelve of the 14 incorrect results were at 5 U/mL (438/450 or 97%), which could be expected near the test cut-off.
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Reproducibility by Lay Users Compared to Professional Readers
A precision study with a three-level precision panel of prepared samples was conducted to evaluate lay user reproducibility. The three levels were targeted to the concentrations of 2, 10 and 15 U/mL to represent negative, low positive and positive values. Five lay readers each conducted assays on two blinded and randomized aliquots of the above samples, resulting in a total of ten results per level. In addition, two professional readers each tested five blinded and randomized replicates of the three-level precision panel, producing 10 results for each level. There was 100% concordance among the lay readers. between professional readers, and between the lay and professional readers. All samples at 2 U/mL were read as negative, and all samples at 10 and 15 U/mL were read as positive.
Performance of Lay Users Compared to Professionals
Field studies to evaluate the ability of lay users compared to professional users of the BladderChek test were conducted at three locations. Each volunteer, aged 50 years or older, some with a history of bladder cancer, tested his or her own urine with one device. At each site professional medical staff re-read the devices used by the lay users, and also conducted their own testing of the volunteers' samples using new devices.
To ensure the presence of some positive results in the study, fourteen samples were spiked with NMP22 to approximately 15 U/mL and fourteen with approximately 25 U/mL. In addition, eight devices were made invalid by not having a working control line.
There was an overall 96.4% concordance between the results obtained by lay users and professional staff reading the same device, and 95.6% agreement between professional and lay users testing the same urine sample on different devices. All spiked specimens were read correctly by lay and professional readers.
| Percent Overall Concordancewith Lay User Result | ||||
|---|---|---|---|---|
| Site 1(N=55) | Site 2(N=35) | Site 3(N=47) | Overall(N=137) | |
| Professional Re-testing of same urinesample with new NMP22 BladderChek™Device | 96.4%(53/55) | 97.1%(34/35) | 93.6%(44/47) | 95.6%(131/137) |
| Professional Re-Read of Lay UserNMP22 BladderChek™ Device | 96.4%(53/55) | 100%(35/35) | 93.6%(44/47) | 96.4%(132/137) |
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Clinical Tests
A prospective clinical trial was performed at 23 sites to determine the utility of NMP22 BladderChek as an aid in monitoring patients with a history of bladder cancer. Voided urine samples were collected from 668 patients prior to surveillance cystoscopy, and clinical staff performed the testing. Physicians conducting the cystoscopies were blinded to the device results.
To determine the sensitivity and specificity, patients were classified as positive or negative for bladder cancer. Patients were considered negative if no tumor was seen endoscopically, or, if a lesion was seen, was pathologically determined to be nonmalignant. There were 291 patients diagnosed as having benign disease(s), and 279 with no evidence of urinary tract disease. Patients were considered positive for bladder cancer if a tumor was seen during cystoscopy, and, if removed was pathologically determined to be malignant. There were 98 recurrences of neoplasms, of which 61 were resected and had stage and grade information available. The remaining 37 patients did not undergo surgical removal, and therefore their tumors could not be staged or graded (Tx, Gx).
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Specificity for individuals with no evidence of disease, benign disease by group, history of non-bladder cancer, and active cancers other than of the bladder is presented in the following table.
| Specificity | (95% CI) | |
|---|---|---|
| Patients with No Evidence ofDisease(History of Bladder Cancer) | 83.9%(234/279) | (79.0%, 88.0%) |
| Benign Diseases* | ||
| BPH/prostatitis | 89.6%(120/134) | (83.1%, 94.2%) |
| Cystitis/inflammation/trigonitis/UTI | 85.2%(23/27) | (66.3%, 95.8%) |
| Erythema | 92.5%(49/53) | (81.8%, 97.9%) |
| Hyperplasia/squamous metaplasia/ cystsand polyps | 82.4%(14/17) | (56.6%, 96.2%) |
| Calculi | 100%(5/5) | (47.8%, 100%) |
| Trabeculations | 89.1%(106/119) | (82.0%, 94.1%) |
| Other benign diseases, kidney andgenitourinary | 86.4%(51/59) | (75.0%, 94.0%) |
| Cancer History, non-bladder -Inactive Other Cancers^ | 88.8%(71/80) | (79.7%, 94.7%) |
| Cancer History, non-bladder -Active Other Cancers^^ | 71.4%(5/7) | (29.0%, 96.3%) |
*Patients may have more than one benign disease
^ Types of cancers: prostate (n=29), skin (n=18), kidney/renal (n=15), genitourinary, non-bladder, non-prostate (n=5), breast (n=6), GI (n=6), lung/respiratory (n=4), blood (n=1), other (n=3).
^ Patients may have more than one type of prior cancer, and current benign diseases. ^^ Types of cancers: prostate (2/4), 1 kidney (0/1), 1 cervical (0/1), 1 lung/liver (0/1)
Sensitivity for patients with bladder cancer was 45.9%. Patients were considered positive for bladder cancer if a tumor was seen during cystoscopy, and, if removed, was pathologically determined to be malignant.
| Cystoscopy | NMP22 BladderChek Test | ||
|---|---|---|---|
| Negative | Positive | Total | |
| Negative | 492 | 53 | 545 |
| Positive | 78 | 45 | 123 |
| Total | 570 | 98 | 668 |
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| Sensitivity(95% Exact CI) | Specificity(95% Exact CI) | Positive PredictiveValue(95% Exact CI) | Negative PredictiveValue(95% Exact CI) | |
|---|---|---|---|---|
| NMP22BladderChek vsCystoscopy | 45.9%(35.8%, 56.3%)(45/98) | 86.3%(83.2%, 89.0%)(492/570) | 36.6%(28.1%, 45.8%)(45/123) | 90.3%(87.5%, 92.6%)(492/545) |
Overall sensitivity and specificity for the clinical trial was as follows.
The NMP22 BladderChek test was more sensitive to later stages and higher grades of cancer, although the majority of malignancies were non-invasive. Sensitivity by stage and grade is detailed in the table below.
| Sensitivity of NMP22BladderChek Test | (95% CI) | |
|---|---|---|
| Tumor stage: Ta- Tl | 40.0%(22/55) | (27.0%, 54.1%) |
| Tumor stage: T2- T3 | 80.0%(4/5) | (28.4%, 99.5%) |
| Tumor stage: Tx | 51.4%(19/37) | (34.4%, 68.1%) |
| Tumor grade: Well differentiated(Grade 1) | 30.0%(9/30) | (14.7%, 49.4%) |
| Tumor grade: Moderately differentiated(Grade 2) | 33.3%(4/12) | (9.9%, 65.1%) |
| Tumor grade: Poorly differentiated(Grade 3 or Grade 4) | 66.7%(12/18) | (41.0%, 86.7%) |
| Tumor grade: Gx(Grade unknown) | 52.6%(20/38) | (35.8%, 69.0%) |
The incidence rate for bladder cancer recurrence in this study was 14.7%. The following table demonstrates the Positive (PPV) and Negative (NPV) predictive values of the NMP22 BladderChek test at varying incidence rates.
| IncidenceRate | NMP22 BladderChek Test | |
|---|---|---|
| Sensitivity=45.9%Specificity=86.3% | ||
| PPV | NPV | |
| 10% | 27.1% | 93.5% |
| 14.7%* | 36.6% | 90.3% |
| 20% | 45.6% | 86.5% |
| 30% | 58.9% | 78.8% |
- Actual incidence rate from NMP22 BladderChek Monitoring Study
Concordance of NMP22 BladderChek and NMP22 Test Kit (microplate)
In comparison testing using voided urine samples, the NMP22 BladderChek Test showed good concordance with the NMP22 Test Kit (microplate).
Voided urine samples were collected from 217 individuals at urology clinics. An aliquot of each sample was applied to a BladderChek Test device. An additional aliquot was stabilized immediately and tested by the Matritech NMP22 (microplate) Test Kit to quantify the NMP22 concentration.
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Overall concordance was 91.2% (198/217, CI 86.7%, 94.7%), with a positive concordance of 87.0% (20/23, CI 66.4%, 97.2%) and negative concordance of 91.8% (178/194, CI 86.9%, 95.2%).
| NMP22 Microplate | NMP22 BladderChek Test | ||
|---|---|---|---|
| Assay | Negative | Positive | Total |
| Negative (≤10 U/mL) | 178 | 16 | 194 |
| Positive (> 10 U/mL) | 3 | 20 | 23 |
| Total | 181 | 36 | 217 |
Conclusion
The NMP22 BladderChek Test and its predicate device, the BTA Stat are technologically similar. The assay reactions (immunochromatography utilizing monoclonal antibodies), sample matrix (voided urine), procedural steps (addition of drops of urine to device), result interpretation (qualitative +/-), patient population (history of bladder cancer), and indication (aid in monitoring), are all similar.
Reproducibility of results with NMP22 BladderChek were excellent between laboratory technicians across lots, days and specimen panel levels. Overall percent of correct reads was 99.2%. A precision study using a prepared specimen panel of negative (2 U/mL). low positive (10 U/mL) and positive (15 U/mL) samples demonstrated 100% concordance between professional staff (n=2) and lay users (n=5). In addition, an investigation to evaluate performance of lay users compared to professional readers showed 96.4% overall concordance when professionals re-read tests performed by lay volunteers using their own urine, and 95.6% when the professionals re-tested the lay users' urine samples. The BTA Stat package insert states that reproducibility studies were performed to determine day-to-day, reader, lot-to-lot, and laboratory-tolaboratory variability. It reports that these studies showed nearly total agreement with the exception of samples near the limit of detection, thus non-clinical performance of the two devices is comparable.
In the prospective clinical trial performed with NMP22 BladderChek sensitivity was 45.9% (CI 35.8%, 56.3%) and specificity was 86.3% (CI 83.2%, 89.0%), with a positive predictive value of 36.6% (CI 28.1%, 45.8%) and a negative predictive value of 90.3% (C1 87.5%, 92.6%). The incidence rate of cancer in the study population was 14.7%. Per its package insert, BTA Stat demonstrated 67% (CI 60%, 73%) sensitivity and 70% (CI 61%, 79%) specificity. Because the performance for this device was determined using retrospective samples selected from a frozen bank, incidence rate could not be determined, so true positive and negative predictive values could not be calculated.
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Using a range of theoretical incidence rates of 10%, 20% and 30%, the NMP22 BladderChek Test demonstrated positive predictive values of 27.1% to 58.9%, compared to 19.8% to 48.8% for BTA Stat. In addition, the overall accuracy (defined as test positive for patients with cancer and test negative for patients without cancer divided by the total number of patients) of NMP22 BladderChek was 80.3% compared to 67.9% for BTA Stat. This was due in part to the excellent specificity of BladderChek, resulting in fewer false positive results.
The non-clinical and clinical studies presented in this submission demonstrate that the clinical utility and performance of NMP22 BladderChek is equivalent or better than that of the predicate device, BTA Stat.
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DEPARTMENT OF HEALTH & HUMAN SERVICES
Image /page/9/Picture/1 description: The image shows the seal of the Department of Health & Human Services USA. The seal is circular, with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" arranged around the perimeter. In the center of the seal is an abstract image of three human profiles facing to the right, with three parallel lines above them. The seal is black and white.
JUL 3 0 2002
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
Melodie R. Domurad. Ph.D. Vice President. Clinical and Regulatory Affairs Matritech, Inc. 330 Nevada Street Newton, Massachusetts 02460
Re: K021231 Trade/Device Name: NMP22® BladderChekTM Test Regulation Number: 21 CFR § 866.6010 Regulation Name: Tumor Marker Test Systems - Monitoring-Bladder Regulatory Class: II Product Code: MMW Dated: June 27, 2002 Received: June 28, 2002
Dear Dr. Domurad:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food. Drug. and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
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Page 2
This letter will allow you to begin marketing your device as described in your 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.
If you desire specific advice for your device on our labeling regulation (21 CFR Part 801 and additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at (301) 594-4588. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at (301) 594-4639. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its internet address "http://www.fda.gov/cdrh/dsma/dsmamain.html".
Sincerely yours,
Steven Sutman
Steven I. Gutman, M.D., M.B.A. Director Division of Clinical Laboratory Devices Office of Device Evaluation Center for Devices and Radiological Health
Enclosure
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INDICATION FOR USE STATEMENT
510(k) Number: K 021231
长021231
Device Name: NMP22® BladderChek™ Test
Indication For Use:
The NMP22 BladderChek test is indicated for use as an aid in monitoring bladder cancer patients, by professional and prescription home use, in conjunction with standard diagnostic procedures.
JP Reeve for S. Altaie
(Division Sign Division of Clinical Laboratory Devices
510(k) Number
(PLEASE DO NOT WRITE BELOW THIS LINE CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of Device Evaluation (ODE)
Prescription Use
(Per 21 CFR 801.109)
OR
Over-The Counter Use
2.1
§ 866.6010 Tumor-associated antigen immunological test system.
(a)
Identification. A tumor-associated antigen immunological test system is a device that consists of reagents used to qualitatively or quantitatively measure, by immunochemical techniques, tumor-associated antigens in serum, plasma, urine, or other body fluids. This device is intended as an aid in monitoring patients for disease progress or response to therapy or for the detection of recurrent or residual disease.(b)
Classification. Class II (special controls). Tumor markers must comply with the following special controls: (1) A guidance document entitled “Guidance Document for the Submission of Tumor Associated Antigen Premarket Notifications (510(k)s) to FDA,” and (2) voluntary assay performance standards issued by the National Committee on Clinical Laboratory Standards.